The nose is a complicated structure that serves dual functions as the organ for the sense of smell and as an entry to the respiratory tract. As part of the respiratory tract, a healthy nose moisturizes and warms incoming air and filters out foreign materials.
Nasal passages and other portions of the respiratory tract are lined with specialized tissue layers. In the nose and sinus areas this tissue is often called the nasal mucosa. Like many tissues, the nasal mucosa is composed of several cell layers and cell types. Mucous cells are one type of cell found in the nasal mucosa. Connected to the nose are sinuses or air-filled cavities located behind certain facial bones. There are four groups of sinuses, namely, frontal, sphenoidal, ethmoidal, and maxillary.
Inflammatory disease of the paranasal sinuses is a common disorder afflicting many people. It is characterized by repeated episodes of inflammation, precipitated initially by environmental factors such as smoke, pollutants or allergens, and often followed by a secondary bacterial infection. Exposure to such environmental inhalants stimulates the first stage of an edematous swelling of the membranes of the nose and a partial blockage of sinus drainage. The stroma becomes hyperemic, edematous and infiltrated with neutrophils, lymphocytes, and plasma cells. Serous and mucinous fluid exudes though the epithelium. Clinically these changes manifest as nasal stuffiness and rhinorrhea. If bacterial infection is superimposed, neutrophils dominate the inflammatory infiltrates that become evident as a thick purulent discharge.
The nose and paranasal sinuses represent the predominant contact point between the respiratory system and our environment. As such, it acts as the primary “filter” to cleanse inspired air prior to the process of respiration in the lower airways. Due to this primary function, it is highly susceptible to physiologic and pathophysiologic inflammation. Two common manifestations of this process include allergic rhinitis (affecting 20% of the population with estimated direct costs of $3.4 billion) and chronic rhinosinusitis (affecting 16% of the population with estimated costs of $5.8 billion). Although both disease processes are very different in clinical manifestations they reflect sinonasal inflammation.
The presence of the inflammatory process in the nasal and paranasal mucosa often gives rise to polyp formation. Persistence of these inflammatory changes leads to infiltration by neutrophils, lymphocytes and eosinophils. These inflammatory sequences of events have been well described in the medical literature and many cells have been implicated in this inflammatory process.
Recent research has shown that the type of nasal inflammation may be determined by the role of various T lymphocytes which may co-exist in a nasal tissue (T van Zele et al, Zhang Nan et al). As review, T-cells belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of specific receptors on their cell surface. It has been shown that in chronic rhinosinusitis with nasal polyps, a deficit in T regulatory cells and the activation of different T effector cells such as Th1, Th2 or Th17 cells exists. These latter cells may orchestrate an inflammatory reaction and also keep T regulatory cells suppressed.
Researchers have begun to consider the effect of cytokine production in nasal inflammation. In particular, interleukins, which are a group of cytokines, are expressed by white blood cells, also known as leukocytes, as a means of communication. Interleukins are produced by a wide variety of body cells. The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. Pro-inflammatory and T cell related cytokines are of particular interest.
Researchers have begun to investigate the role of transforming growth factor beta (TGF-β) in sinus inflammation (N van Bruaene et al). TGF-β is known to control proliferation, cellular differentiation, and other functions in most cells. It plays a role in immunity, cancer, heart disease and Marfan syndrome. Some cells secrete TGF-β, and also have receptors for TGF-β. This is known as autocrine signaling. Cancerous cells increase their production of TGF-β, which also acts on surrounding cells. TGF-β is a secreted protein that exists in three isoforms called TGF-β1, TGF-β2 and TGF-β3. The TGF-β family is part of a superfamily of proteins known as the transforming growth factor beta superfamily, which includes inhibits, activin, anti-müllerian hormone, bone morphogenetic protein, decapentaplegic and Vg-1.
Existing treatments of nasal and sinus inflammation includes the use of antibiotics, both systemic and topical anti-inflammatory agents and decongestants. More recently, topical steroid sprays have been introduced as well as cromolyn which intervenes in this inflammatory process and produces clinical improvement in some of these patients. Unfortunately, many of these patients continue to have advancing disease that leads to total obstruction and a chronic sinusitis. These patients ultimately undergo surgical intervention. The classical surgical techniques involve radical exoneration of polyploid tissue from the nose and paranasal sinuses and the establishment of proper drainage. Such surgery is performed in the hospital under general anesthesia where a fair amount of bleeding is encountered along with some morbidity, not to mention the surgical risks of ocular and intracranial complications of such an extensive sinus surgery.
Other treatments developed over the last two decades have included investigating the mechanism of action of many long time practiced herbal therapies. Many attempts to identify the active components of herbal remedies have concluded that in general no one component is responsible for the therapeutic capacity, but rather the complex and intricate interactions of the herbs result in therapeutic efficacy. Additionally, many of these herbal combinations have demonstrated anti-inflammatory actions. Although the majority of herbal medications are delivered orally, topical applications have also been practiced. Thus, the prospect of managing nasal and paranasal sinus inflammation with topical applications of medicinal herbal extracts is promising.
Recently Jung et al published their findings demonstrating robust reduction of inflammatory parameters, including IL-6, TNF-a, neutrophil density and prostaglandin E2 in the mouse airpouch inflammatory model with root extracts from traditional oriental medicinal plants. Many of these parameters are also found to be increased in Rhinologic diseases. Thus, a topical preparation of herbal extracts and antioxidants were prepared for evaluation. However, prior to confirmation of the anti-inflammatory properties of the extract in a rhinologic model, the preparation should be demonstrated to be safe as a topical application in the nose. Additionally, since bacterial colonization/infection is believed to contribute to the persistent inflammation associated with Rhinosinusitis, antibacterial activity of the preparation should also be undertaken.
Therefore, it would be advantageous to provide an herbal-based solution for a nasal solution that targets and affects specific T effector cells and TGF-β present in the nasal tissue in order to maintain long-term inhibition of sinus inflammation.